Mycoplasma genitalium is a newly recognized cause of reproductive tract disease syndromes, including urethritis, mucopurulent cervicitis, pelvic inflammatory disease, endometritis, preterm birth, with possible sequelae that include infertility, chronic pelvic pain, preterm birth, and enhanced cervical shedding of HIV. Studies assessing the pathogenesis, immunobiology, and virulence factors of M. genitalium are currently being performed in several laboratories, yet are limited by the lack of an appropriate animal model. Chimpanzees, which are no longer available for experimental studies, have been previously used to demonstrate the ability of M. genitalium to cause disease and persist in the urethra, vagina, cervix, and oviducts of these animals. Although other primate species have been less extensively studied, M. genitalium has persistently infected, produced characteristic disease, and induced an antibody response in the majority of species tested. The availability of the Washington National Primate Research Center (WaNPRC) housed at the University of Washington, the availability of the cervical infection model of pigtailed macaques (Macaca nemestrina) developed by Dr. Patton, a co-investigator on this application, provides a unique opportunity to study the immunopathogenesis of M. genitalium infection. Dr. Totten's research demonstrating the disease associations of M. genitalium, the possible role of antigenic variation in the ability of this organism to persist in infected women, and her proven ability to culture this fastidious organism, provide the necessary expertise to study the molecular pathogenesis of this novel organism. We thus propose to assess the pigtailed macaque cervical infection model to evaluate infection and persistence of M. genitalium, the innate and adaptive immune response to this organism, and the role of antigenic variation in allowing M. genitalium to evade the antibody response and persist. PUBLIC HEALTH RELEVANCE: These studies will further our understanding of the immunobiology of infection and the possible mechanisms used by M. genitalium to cause disease and persist. Further establishment and characterization of this model will lead to future studies assessing the pathogenesis of M. genitalium as well as the evaluation of effective strategies for prevention and treatment.